SU11248对白血病细胞HL-60增殖及凋亡作用的实验研究  

Effect of SU11248 on proliferation and apoptosis of leukemia cell line HL-60

作　　者：陈惠瑜[1] 施腾飞[2] 成玲[1] 林东红[3] 罗玲清[4] 胡建达[5] 

机构地区：[1]福建省妇幼保健院检验科,福州350001 [2]福州市第二医院检验科,福州350007 [3]福建医科大学医学与技术工程学院检验系,福州350004 [4]福建省肿瘤医院检验科,福州350001 [5]福建医科大学附属协和医院血液病研究所,福州350001

出　　处：《中国免疫学杂志》2012年第6期512-516,共5页Chinese Journal of Immunology

基　　金：福建省教育厅科技项目(JA07085);福建医科大学教授基金资助项目(JS08009)

摘　　要：目的:探讨新型抗肿瘤药物苹果酸舒尼替尼(SU11248)对白血病细胞HL-60的生物学效应的影响及其作用机制。方法:应用MTT法检测SU11248对HL-60细胞增殖能力的影响;用AnnexinV/PI双染流式细胞术检测细胞凋亡;用流式细胞技术分析细胞的DNA倍体及细胞周期变化;用凝胶电泳分析DNA片段化;以Western blot法检测2.0μg/ml SU11248作用HL-60后bcl-2、bax、caspase-3蛋白水平的变化。结果:SU11248可明显抑制HL-60细胞增殖(P<0.05),呈剂量和时间依赖性,半数抑制浓度(IC50)约为2.00μg/ml。SU11248可促进细胞凋亡,并呈剂量依赖性;能将HL-60细胞阻滞于G0/G1期,并呈时间依赖性;诱导HL-60细胞呈典型的DNA梯带;SU11248作用后bcl-2蛋白表达随时间依赖性降低,caspase-3蛋白表达升高,bax蛋白表达无明显变化。结论:SU11248能抑制HL-60细胞增殖,诱导其凋亡,调节bcl-2家族蛋白的表达,并裂解caspase-3是其可能作用机制之一。Objective：To investigate the effect of a new antineoplastic agent SU11248 on proliferation and apoptosis of leukemia cell line HL-60 in vitro and analyze its mechanisms.Methods：Effect of SU11248 on proliferation of HL-60 cells was detected by MTT assay.The ability of SU11248 to induce apoptosis of HL-60 cells was examined by AnnexinV/PI,DNA ploidy and cell cycle analysis of HL-60 cells was detected by flow cytometry techniques;DNA fragmentation was utilized by gel electrophoresis techniques.Expression of bcl-2,bax and casp ase-3 in HL-60 was assessed by Western blot assay.Results：The proliferation of HL-60 cells was inhibited by SU11248 in dose-and time-dependent manners（P〈0.05）.The concentration of 50% growth inhibition（IC50）of SU11248 for HL-60 was 2.0 μg/ml.HL-60 was blocked in G0/G1 phase and induced apoptosis by SU11248.After treating HL-60 cells with 2.0 μg/ml SU11248 at different time points,expression of bcl-2 was reduced and caspase-3 was increased significantly in a time dependent manner,but bax changed little.Conclusion：SU11248 inhibited HL-60 cells growth and induced apoptosis with the reduction of bcl-2/bax protein expression and cleavage of caspase-3.

关 键 词：SU11248 白血病 HL-60细胞 凋亡 

分 类 号：R392[医药卫生—免疫学]